Advertisement

Advertisement

Flu drugs work and are needed during pandemics

By Debora Mackenzie

(Image: Chris Radburn/PA)

The flu drugs Tamiflu and Relenza are likely to be effective at preventing deaths in flu pandemics, an independent committee of experts has said. Their review of the drugs was launched in response to claims that stockpiles of antivirals, set up in case of a pandemic, are a waste of money.

Campaigners have said there is no proof that Tamiflu (oseltamivir) and Relenza (zanamivir) are any more help against flu than a stiff whisky, citing evidence from clinical trials of the drugs in ordinary winter flu, which showed they only slightly reduced the duration of illness.

Advertisement

However, the independent committee, launched by the UK Academy of Medical Sciences and the Wellcome Trust charitable foundation, has found that such clinical trials “cannot simply be extrapolated to an epidemic or pandemic situation” in which severe flu is more common. The committee says that other studies, in which the drugs have been used to combat more severe flu, have shown them to be useful in reducing deaths.

To stock or not

Britain has spent £560 million, the US has spent $1.3 billion and Australia has spent $A192 million on antiviral stockpiles for flu, and the drugs are due for renewal.

The review did not comment on the stockpiles, because it said other factors besides science determine government policy. However, it did state that “should a circulating pandemic or seasonal strain result in greater prevalence of infection or severity of symptoms, the routine use of (these drugs) for all patients with influenza might become advisable”.

“Personally I think it is absolutely right to stockpile,” says Jeremy Farrar, a member of the review team and head of the Wellcome Trust. If a deadly flu pandemic hit, he says, “and you know the drugs reduce deaths in hospitalised individuals, it is unthinkable that the government would have no access to it”.

An ongoing debate

So why was the review needed? Questions about the use of antiviral drugs were raised in 2009 by a group working for the Cochrane Collaboration, a research network that evaluates evidence for medical treatments. They reviewed randomised controlled clinical trials by the drugs’ manufacturers, Swiss firm Roche, and UK-based GSK, in which otherwise healthy adults with ordinary winter flu got the drug or a placebo, and found the drugs only reduced duration of illness slightly.

However, these researchers also highlighted a study of the 2009 swine flu pandemic led by Jonathan Nguyen-Van-Tam at the University of Nottingham, UK, which showed that the drugs reduced the chance of people dying of viral pneumonia, which is common in pandemics, but rare in ordinary flu. Cochrane rejected that research because it was an observational study, without a placebo or randomisation.

Researchers from the review committee said that Nguyen-Van-Tam’s study was valid. They also rejected claims that it shouldn’t be considered because Roche funded it, as the funding was at “arm’s length”.

They found that the trials that Cochrane relied on could not address whether the drugs are effective in a pandemic, because the information did not reflect what happens during a typical pandemic. For example, it included very few severely ill patients, few hospitalisations and no deaths.

Quick off the mark

To really resolve the question, however, the review committee recommended designing randomly controlled trials now for these antivirals, which can be launched quickly when a pandemic strikes. Some people have questioned whether it is ethical to put severely ill patients on a placebo given the evidence that the drugs work, but Chris Butler at the University of Oxford, a member of the review committee, says new, innovative trial designs would allow patients to be switched to effective treatment quickly if favourable evidence starts emerging from the trials.

He is starting a randomised study of the effectiveness of antivirals on ordinary flu that he hopes could be quickly scaled up should a pandemic strike while he’s doing the work over the next three years.